Gene duplication is a key source of genetic novelty, which in the best case leads to the acquisition of advantageous phenotypes, and in the worst results in disease. Functional duplicate genes can be maintained in the genome via three distinct processes: 1) the acquisition of a novel function in one copy (neofunctionalization), 2) the division of ancestral functions among copies (subfunctionalization), or 3) the preservation of ancestral functions in all copies (conservation). Despite the importance of gene duplications in both evolution and disease, little is known about the relative frequencies or mechanisms of each of these processes. To address these questions, this proposal will utilize complementary high-throughput experimental and computational approaches to investigate the correlated sequence and expression evolution of duplicate genes in three closely-related species of Drosophila. In particular, this project is subdivided into three specific aims. First, it will identify recent gen duplications via comparative genome analysis of three closely-related species of Drosophila. Second, it will use gene expression as a proxy for function to disentangle the processes of neofunctionalization, subfunctionalization, and conservation in the maintenance of young duplicate genes in Drosophila. Third, from intra-species polymorphism data, it will infer the evolutionary forces driving each of these processes. Due to the central role Drosophila has played as a model organism in genetic research, findings from this study will likely be applicable to a wide range of organisms, enhancing our understanding of both the evolution of novel phenotypes and the genetic basis of duplication-associated human diseases. PUBLIC HEALTH RELEVANCE: Gene duplication, which produces two copies of a gene in an individual's genome, can lead to the acquisition of novel character traits or phenotypes. If the resulting phenotype is beneficial, it can lead to the evolutionary diversification of species; otherwise, it can cause one of hundreds of diseases, including Alzheimer's, heart disease, and cancer. Thus, knowledge about how gene duplication results in new phenotypes is crucial to our understanding of both evolution and human disease.